The goal to reduce the ionizing radiation dose burden from medical imaging has gained substantial visibility in recent years, however we require evidence to change current practice guidelines as substantial change in dose of the imaging radiopharmaceutical can affect image quality, quantitative readouts and diagnostic confidence. PET/CT using 18F-FDG is an essential imaging procedure for oncologic diagnosis and assessment of therapeutic interventions. While current studies are exploring low dose CT techniques for the attenuation scan, this innovative Phase I trial will test and validate low FDG dosing compared to current standard of care PET/CT. In Aim 1, we want to validate the diagnostic equivalency of current standard of clinical care FDG dosing to a 60% reduced dose level by an intra-individual crossover designed trial performed as individual sub-studies on four different state-of-the-art PET/CT systems. In Aim 2, we will validate that such a dose reduction of PET tracer does not alter the detectability of uptake changes by comparing a whole-body scan performed at 60 min post injection with that at 75 min p.i. At the same time, we will assess the variations that can be found intra-individually within this time window, an important consideration for clinical trials that use FDG PET to assess response. In Aim 3, we will validate the equivalence between simulated and actual low dose PET scans performed. Our preliminary data show that simulation of lower dose PET images derived by segmented reconstruction of standard dose acquired PET scans is valid and predictive for phantom experiments, and should be able to emulate clinical scans at lower dose levels. Once such a simulation approach is validated, we can simplify PET tracer dose finding studies and guide clinical practice for tracer dose optimizations. As the ability to substantially reduce dose can be impacted by vendor specific PET/CT system designs, we will perform sub-studies, using both the current generation systems from the three major manufacturers and the first available next generation digital detector system. Our overall goal is to radically reduce the FDG dose in current standard of care and clinical trial protocols for oncologic imaging validated by a prospective trial and thereby enabling to substantially reduce the radiation burden to patients and associated caretakers without impacting diagnostic and quantitative capabilities.